Exercise and physical activity in people with dust-related respiratory diseases

Abstract

Non-malignant dust-related respiratory diseases are a global health problem, with some asbestos-related diseases now pandemic. Millions of people continue to be exposed to harmful substances such as asbestos, silica and coal, despite the known deleterious effects. There are many manifestations of dust-related respiratory diseases (a term encompassing all dust-related diseases of the respiratory system) and are characterised by the type of inhaled ‘dust’ or particulate matter, and the location of the disease in the respiratory system (i.e. in the lung interstitium or pleura). The location of the disease can be distinguished using two terms: ‘dust-related interstitial lung disease’ referring to diseases occurring in the lung interstitium, including asbestosis, silicosis and other pneumoconioses and ‘asbestos related pleural disease’ (ARPD) referring to asbestos-related diseases of the pleura such as diffuse pleural thickening (DPT), rounded atelectasis and asbestos-related pleural effusion (which commonly precedes DPT). People with pleural plaques as the only manifestation of ‘dust’ exposure, as well as people with mesothelioma and asbestos-related cancer, were excluded from the studies in this thesis. Little is known about whether functional exercise capacity or physical activity (PA) levels are reduced in people with dust-related respiratory diseases, or whether exercise training is beneficial in the disease management. In healthy people and those with chronic respiratory diseases, higher levels of exercise capacity and PA have been shown to be important in maintaining health. Recent consensus documents recommend that all people with a chronic respiratory disease be considered for pulmonary rehabilitation (PR), of which exercise training is the major component. However, no studies have evaluated functional exercise capacity or PA levels in people with dust-related respiratory diseases. Furthermore, no randomised controlled trials (RCTs) have examined whether exercise training is beneficial in people with dust-related respiratory diseases, or whether the effects of exercise training differ in people with dust-related interstitial lung disease (ILD) and ARPD. The series of studies contained in this thesis, involving people with dust-related respiratory diseases including asbestosis, silicosis, mixed-dust pneumoconiosis and ARPD, aimed to 1) determine whether functional exercise capacity and health-related quality of life (HRQoL) were reduced in people with ARPD; 2) determine whether PA levels in people with ARPD and dust-related ILD were reduced in comparison to an age- and gender-matched healthy control group; 3) evaluate in a RCT the short- and long-term effects of exercise training on exercise capacity and HRQoL compared to usual medical management in people with dust-related respiratory diseases; 4) evaluate the effects of exercise training in people with dust-related respiratory diseases compared with control, placebo or another non-exercise intervention and determine whether the effects of exercise training in people with dust-related ILD differed from the effects of exercise training in people with ARPD by performing a systematic review of the literature to synthesise data from RCTs. To achieve these aims, the thesis contains a literature review, a methods chapter and four research studies. The literature review presented in Chapter 1 provides a background on the various non-malignant dust-related respiratory diseases and the impact of these diseases on exercise capacity, HRQoL and PA, as well as discussing the literature on exercise training in dust-related respiratory diseases and other ILDs. Chapter 2 provides detailed methodological procedures for the studies reported in Chapters 3, 4 and 5. The observational study in Chapter 3 examined functional exercise capacity and HRQoL in people with ARPD. The main findings were that people with ARPD have reduced functional exercise capacity measured by the six-minute walk test (6MWT) with mean (standard deviation (SD)) of 76 (11)% predicted and reduced HRQoL measured by the St George’s Respiratory Questionnaire (SGRQ) (mean (SD) Symptoms 29 (21) points; Activity 34 (22) points; Impacts 15 (14) points; Total score 23 (15) points). The observational study in Chapter 4 measured PA levels in people with ARPD and dust-related ILD and compared these to PA levels in an age- and gender-matched healthy control group. The main finding was that the dust-related ILD participants were significantly less active compared to the healthy participants as measured by: 1) steps per day with a mean difference (MD) (95% confidence interval (CI)) between healthy and dust-related ILD participants of 4533 steps per day (1888 to 7178 steps per day) and 2) energy expenditure (EE) with a MD (95% CI) of 512 calories per day (196 to 827 calories per day). Dust-related ILD participants also spent significantly less time engaging in activities at or above a moderate intensity (i.e. > 3 metabolic equivalents (METs)) compared to healthy participants (MD (95% CI) 1.2 hours per day (0.45 to 2.0 hours per day)). Furthermore, dust-related ILD participants were significantly less active in all PA outcomes compared to participants with ARPD. Physical activity was not reduced in people with ARPD when compared to an age- and gender-matched healthy control group. The RCT in Chapter 5 investigated the short- and long-term effects of exercise training on exercise capacity and HRQoL compared to usual medical management in people with dust-related respiratory diseases. A secondary aim was to determine whether exercise training improved PA levels compared to usual medical management. The main findings were that exercise training improved short- and long-term exercise capacity and HRQoL compared to usual medical management. Specifically, for six-minute walk distance (6MWD) there was a MD (95% CI) between groups in favour of the exercise training group of 53 metres (32 to 74 metres) immediately following exercise training and 45 metres (17 to 73 metres) at the 26-week follow-up after completion of exercise training. Immediately following exercise training in the SGRQ Total score, the MD (95% CI) between groups was -7 points (-13 to -1 points) in favour of the exercise training group and in the Chronic Respiratory Disease Questionnaire (CRQ) Total score there was a MD (95% CI) of 6.4 points (2.1 to 10.7 points) in favour of the exercise training group, both indicating improved HRQoL. The improvement in CRQ Total score in the exercise training group was maintained at the 26-week follow-up with a MD (95% CI) between groups of 13.1 points (5.2 to 20.9 points). For the secondary outcome of PA levels, there was a MD (95% CI) between groups in favour of the exercise training group of 1514 steps per day (15 to 3012 steps per day) and 0.08 average daily METs (0.01 to 0.15 average daily METs) immediately following exercise training. The improvement in average daily METs in the exercise training group was maintained at the 26-week follow-up with a MD (95% CI) between groups of 0.11 average daily METs (0.03 to 0.20 average daily METs). However, as the magnitude of the improvements in average daily METs was very small in the short- and long-term, the clinical relevance of these findings is unclear. The Cochrane systematic review with meta-analyses in Chapter 6 was designed to evaluate the effects of exercise training compared with control, placebo or another non-exercise intervention in people with dust-related respiratory diseases and to determine whether the effects of exercise training in people with dust-related ILDs differed to the effects of exercise training in people with ARPD. Data from only two RCTs were suitable for inclusion in the meta-analyses. One RCT was the study presented in Chapter 5, and the other data were from five participants with asbestosis who were part of a larger RCT in a heterogeneous group of people with ILD. The meta-analyses demonstrated that immediately following exercise training, 6MWD increased in the exercise training group with a MD (95% CI) between groups of 53.81 metres (34.36 to 73.26 metres) compared with the control group of no exercise training. Six months following exercise training, the MD (95% CI) between the exercise training and the control groups was 52.68 metres (27.43 to 77.93 metres) in favour of the exercise training group. Immediately following exercise training, improvements were demonstrated in HRQoL in the exercise training group compared with the control group, in the CRQ domains of Dyspnoea, Fatigue, Emotional Function and Mastery. Six months following exercise training, improvements in the CRQ domains of Dyspnoea, Emotional Function and Mastery were maintained in the exercise training group. Subgroup analyses showed that improvements following exercise training were similar in participants with dust-related ILD and in participants with ARPD compared to the control group, with no statistically significant differences in treatment effects between participants with dust-related ILD and ARPD. A summary of the main findings of the thesis is presented in Chapter 7, along with a discussion of the clinical implications of the findings and suggestions for future research. Overall, the series of studies in this thesis have demonstrated that exercise capacity and HRQoL are reduced in people with ARPD, and that PA levels are reduced in people with dust-related ILD but not in people with ARPD. Importantly, there is now evidence for the benefits of exercise training in people with dust-related respiratory diseases.